Genome-wide association study of liver fat, iron, and extracellular fluid fraction in the UK Biobank

Abdominal magnetic resonance imaging (MRI) represents a non-invasive approach allowing the extraction of clinically informative phenotypes. We developed an automated pipeline to segment liver pixels from abdominal MRI images and apply published models to approximate fat fraction, extracellular fluid fraction and iron content in 40,058 MRIs from the UK Biobank. We then conducted a genome-wide association of these traits using imputed variants (N=37,250 individuals, 11,914,698 variants) and exome sequence data (N=35,274 individuals, 8,287,315 variants). For liver fat we identified 8 novel loci in or near genes MARC1, GCKR, ADH1B, MTTP, TRIB1, GPAM, PNPLA2 and APOH. For liver iron we identified 1 novel locus between the genes ASNSD1 and SLC40A1, an iron transporter involved in hemochromatosis. For extracellular fluid fraction we identified 6 novel loci in or near genes AGMAT, NAT2, MRPL4-S1PR2, FADS1, ABO and HFE, with almost all having prior associations to obesity, liver, iron, or lipid traits.

The composition of subduction zone fluids and the origin of the trace element enrichment in arc magmas

The partitioning of major and trace elements between eclogite and aqueous fluids with variable salinity was studied at 700–800 °C and 4–6 GPa in piston cylinder and multi anvil experiments. Fluid compositions were determined using the diamond trap technique combined with laser ablation ICP-MS measurements in the frozen state. In addition to NaCl, SiO2 is the main solute in the fluids. The fluid/eclogite partition coefficients of the large ion lithophile elements (LILE), such as Rb, Cs, Sr, and Ba as well as those of the light rare earths (LREE), of Pb, and of U increase by up to three orders of magnitude with salinity. These elements will therefore be efficiently transported by saline fluids. On the other hand, typical high field strength elements, such as Ti, Nb, and Ta, are not mobilized even at high salinities. Increasing temperature and pressure gradually increases the partitioning into the fluid. In particular, Th is mobilized by silica-rich fluids at 6 GPa already at low salinities. We show that we can fully reproduce the trace element enrichment pattern of primitive arc basalts by adding a few percent of saline fluid (with 5–10 wt% Cl) released from the basaltic slab to the zone of melting in the mantle wedge. Assuming 2 wt% of rutile in the eclogite equilibrated with the saline fluid produces a negative Nb Ta anomaly that is larger than in most primitive arc basalts. Therefore, we conclude that the rutile fraction in the subducted eclogite below most arcs is likely < 1 wt%. In fact, saline fluids would even produce a noticeable negative Nb Ta anomaly without any rutile in the eclogite residue. Metasomatism by sediment melts alone, on the other hand, is unable to produce the enrichment pattern seen in arc basalts. We, therefore, conclude that at least for primitive arc basalts, the release of hydrous fluids from the basaltic part of the subducted slab is the trigger for melting and the main agent of trace element enrichment. The contribution of sediment melts to the petrogenesis of these magmas is likely negligible. In the supplementary material, we provide a “Subduction Calculator” in Excel format, which allows the calculation of the trace element abundance pattern in primitive arc basalts as function of fluid salinity, the amount of fluid released from the basaltic part of the subducted slab, the fluid fraction added to the source, and the degree of melting.

Increasing age is independently associated with higher free water in non-active MS brain - A multi-compartment analysis using FAST-T2

PurposeTo explore the relationship between the cerebral cortical perivascular space (PVS) and aging in non-active MS subjects by using the multi-echo T2 relaxometry based cerebrospinal fluid fraction (CSFF) map.MethodsMulti-echo spiral T2 data from 111 subjects with non-active multiple sclerosis (MS) were retrospectively investigated by fitting the T2 data into a three-compartment model, the three water compartments including myelin water, intra-extracellular water, and cerebrospinal fluid. Segmentation of T1w image was performed to get the region of interest (ROI) in cerebral cortical regions. The white matter lesion segmentation was conducted using a convolutional neural network (CNN) based segmentation tool. The CSFF in the ROIs were correlated with age by controlling the gender, white matter hyperintensity lesion burden, and MS disease duration. Multiple linear models were created for the analysis of aging effect on the CSFF.ResultsThe ROI analysis shows that the CSFF in the cerebral cortical regions (temporal, occipital, parietal, front, hippo, and mtl) are significantly linear increasing with age (p<0.01). The intra-extracellular water fraction (IEWF) in the ROIs are significantly linear decreasing (p<0.01).ConclusionThe multi-echo T2 based three-compartment model can be used to quantify the CSFF. The linear increase of CSF water contents in the cerebral cortical regions indicates increased perivascular space load in cortex with aging. The quantification of CSFF may provide a way to understand the glymphatic clearance function in aging and neurodegenerations.HighlightsMR T2 relaxometry is a valid method to quantify the cerebrospinal fluid fraction (CSFF) in cerebral cortical regionsThe CSFF in the cerebral cortical regions are positively correlated with age by controlling the white matter lesion load in non-active MS subjects.Quantification of cerebral CSFF may reflect the perivascular space load in cortex and better interpret the disease progression in neurodegenerative disease, such as MS.

Vibration Reduction Performance of Damping-Enhanced Water-Lubricated Bearing Using Fluid-Saturated Perforated Slabs

As the first link element for the transmission of shaft vibration to the pedestal and even to the hull, water-lubricated bearing plays a key role in suppressing vibration. Although the porous structure is considered as one of the main methods for improving the wideband vibration and noise reduction performance of materials in many industrial fields, the studies in the field of water-lubricated bearing remain insufficient. To enhance vibration reduction performance, a fluid-saturated perforated slab is designed in this study, and via the establishment of a fluid-solid coupled vibration model, the influence law and impact levels were analyzed and verified by simulation and experiments. The results obtained verified that the total vibration amplitude of damping-enhanced stern bearing in the vertical direction was smaller than that of the normal stern bearing, and the reduction amplitude of the characteristic frequency agreed with the optimal value at approximately 0.1 of the volume fraction of the liquid phase when the solid-fluid phase was rubber–water. Additionally, the increase in fluid fraction did not enhance the damping effect, instead, it unexpectedly reduced the natural frequency of the raw material significantly. This research indicates that the design of the fluid-saturated perforated slab is effective in reducing the transmission of the vibration amplitude from the shaft, and presents the best volume fraction of the liquid phase.

EFFICIENCY OF ANTIOXIDANTS IN INTEGRATED THERAPY OF ACUTE ODONTOGENIC OSTEOMYELITIS IN CHILDREN

This paper presents the comparative generalization of the results obtained by studying the activation of the processes of lipid peroxidation and the state of antioxidant protection factors in the peripheral blood and unstimulated oral fluid fraction in patients having a complicated course of odontogenic mandibular osteomyelitis. To determine the effectiveness of natural antioxidants, which were additionally included in the therapy protocol for patients with this the disease, we created two similar groups of participants (22 and 23 people in each) aged 7 to 15 years. Based on our previous reports, on admission to the hospital, these patients demonstrated the activation of the lipid peroxidation processes and the reduction of antioxidant protection factors in biological substrates. The scope of the treatment measures described in the protocol did not allow us to normalize their components for the time of clinical recovery. This prompted us to prescribe tocopherol acetate and ascorbic acid as components of the integrated complex therapeutic measures. This helped to stabilize the levels of all indicators up to the time of clinical recovery in this group of patients and supported the feasibility of these pharmaceuticals as important components in the therapy of odontogenic inflammatory diseases.

PROCESSES OF LIPID PEROXIDATION AND ANTIOXIDANT PROTECTION IN ACUTE ODONOGIC OSTEOMYELITIS IN CHILDREN

The paper presented summarizes the results on the parameters of free radical lipid oxidation and antioxidant protection factors in 24 children aged from 3 to 15 years with acute odontogenic mandible osteomyelitis. In addition to standard clinical examination, peripheral blood and unstimulated oral fluid fractions were collected from all patients for 10 min at hospital admission and discharge. The samples were used to determine the components of lipid peroxidation: diene conjugates; malondialdehyde, its initial level, in 1.5 hours of incubation and its growth; antioxidant protection factors as superoxide dismutase, and catalase. It has been found out at the time of hospitalization, clinical examination showed a significant deterioration of the general condition, which was accompanied by widespread infiltrative changes and collateral oedema in the projection of the involved region of the mandible. In 12 people (50%) osteomyelitis spread from temporary molars. In other cases, permanent first and second molars were regarded as the causes. The patients demonstrated the activation of lipid peroxidation processes and reduction of antioxidant protection factors found out in peripheral blood and unstimulated oral fluid fraction. Repeated studies over the clinical recovery following the treatment conducted in accordance with the protocol of medical care enables to estimate the absence of infiltrative changes, but despite the elimination of acute inflammation, not all the studied parameters reached the level of control values. This makes it necessary to address the issue on making corrections towards the complex of therapeutic measures by including antioxidants that seems to be quiet promising and requires further in-depth investigation.

Epidote dissolution and its role within carbon storage

&lt;p&gt;In the past 20 years, basaltic aquifers have been studied as a key geologic carbon storage host due to their high reactivity and widespread distribution. However, many basaltic reservoirs contain substantial alteration minerals and their potential as cation sources for carbon mineralization processes still need to be assessed. A common alteration phase in high temperatures (&amp;#8805; 200 &amp;#176;C) basalts is epidote. To help determine the possible contribution of this mineral to CO2 sequestration through the release of its constituting cations, the dissolution rates of epidote from the Green Monster Mine (Alaska) were experimentally measured. Far-from equilibrium experiments were conducted over the pH range 2-11 using both batch reactors at 25 &amp;#176;C, and mixed-flow reactors at 100 and 200 &amp;#176;C. Furthermore, mixed-flow reactor experiments at pH ~9 on epidote in presence of CO2 were carried out at 200 &amp;#176;C to study its carbonation potential and to quantify the yields of this reaction compared to basaltic glass. The determination of the extent of this process was monitored by inorganic carbon analyses on both solid and fluid fraction using non-dispersive infra-red (NDIR) CO2 gas analyses. Preliminary results suggest that epidote and potentially other alteration Ca-silicate phases can provide Ca2+ as efficiently as fresh basalts at 25 and 100 &amp;#176;C to promote the precipitation of calcium carbonate. Further experimental and modelling work is ongoing to confirm these findings at different thermal conditions and as a function of injected fluid chemistry.&lt;/p&gt;

Antimicrobial properties of the peptide substance Bacillus Subtilis PSF-19

The subject of the study is a strain of Bacillus subtilis PSF-19 isolated by us from vegetable raw materials (Passiflora preparation), which is capable of producing antimicrobial substance (AMV) suppressing pathogenic bacteria. The article discusses the method and conditions of extraction from the culture fluid fraction of AMV, active against Listeria monocytogenes – one of the dangerous intestinal pathogens that infect food. Using biochemical methods and mass spectroscopy, the molecular weight and the peptide nature of the active fraction of AMV were determined. A fraction of AMV with a molecular weight of 3,4–3,6 kDa has bactericidal activity, which is destroyed by treatment with proteolytic enzymes, which allowed it to be attributed to the group of low-molecular antimicrobial peptides – bacteriocins. The studies allow to consider the strain Bacillus subtilis PSF-19 as a producer of bacteriocin, especially effective against pathogens of intestinal listeriosis. The establishment of the fact of destructibility of proteolytic enzymes, finding the conditions of microbiological synthesis of AMV, its isolation and accumulation for research, provide opportunities for practical use as a means for decontamination of the environment instead of traditional antibiotics.